NCOR1
protein-codingnuclear receptor corepressor 1, the group of NCoR/SMRT transcriptional repression complex subunits|Myb/SANT domain containing|Protein phosphatase 1 regulatory subunits
Gene summary
This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 17 and 20.[provided by RefSeq, Jun 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~189.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NCOR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006311.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 28 | 13 | 45 | ||
| missense | 1 | 260 | 12 | 3 | 276 | |
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 19 | 19 | ||||
| Total | 0 | 1 | 290 | 40 | 16 | 347 |
Highest pathogenic variant AF is 0.000026247999
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006302.2 | 45 | MANE Select | |
| Ensembl | ENSP00000268712.2 | 45 | MANE Select | |
| RefSeq | NP_001177367.1 | 19 | Standard | |
| RefSeq | NP_001177369.1 | 45 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ncor1 | Danio rerio | Structure: neutrophil Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thyroid hormone signaling pathway - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Androgen receptor signaling pathway
- Adipogenesis
- Ovarian Infertility Genes
Biological Process
- negative regulation of transcription by RNA polymerase II
- chromatin organization
- transcription by RNA polymerase II
- circadian rhythm
- regulation of lipid metabolic process
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II regulatory region DNA binding
- RNA polymerase II activating transcription factor binding
- chromatin binding
- transcription corepressor activity
Cellular Component
- histone deacetylase complex
- nuclear chromatin
- nucleus
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268712
- Coding exons
- 45
- Length
- 189029
- Individuals with no LoFs
- 125643
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 105
- Defined
- 125748
- p
- 0.000418
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.94 | 940 | 1.35e+3 | 0.698 | 0.0000753 | 15835 |
| Missense (PolyPhen) | 398 | 668.3 | 0.59554 | 7762 | ||
| Synonymous | 0.430 | 470 | 482 | 0.975 | 0.0000274 | 4838 |
| Loss of Function | 9.44 | 15 | 132 | 0.114 | 0.00000780 | 1493 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00098 | 0.00098 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.0020 | 0.0020 | notable |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). {ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}.;
Recessive Scores
- pRec
- 0.625
Intolerance Scores
- LoFtool
- 0.467
- RVIS EVS
- -2.14
- RVIS percentile EVS
- 1.5
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |